"Out-of-the-box" new method stops bacteria spreading antibiotic resistance – without killing them
There's a never-ending war going on all around us, down at the microscopic level. Bacteria and viruses are locked in battle against each other – and us, as we try to clear them out with antibiotics. But we might be losing the war, as the bugs rapidly develop resistance to our best drugs. Now researchers from Washington University in St. Louis have found a way to potentially prevent bacteria from spreading antibiotic resistance to each other.
Bacteria become resistant to antibiotics in a few main ways. For one, whenever the drugs wipe out a colony a few particularly hardy individuals survive, and when they then duplicate they pass on their genetic antibiotic resistance to their offspring. Over time, that means the population as a whole becomes immune to the drugs.
The second method is more insidious. Bacteria are also capable of horizontal gene transfer, meaning they can pass certain genes to each other like kids passing notes to cheat in a test. In this case, the "notes" are small snippets of DNA known as plasmids, and one trick they can pass on is antibiotic resistance.
"Plasmids want to take over the world," says Mario Feldman, senior author of the study. "Plasmids are selfish genetic elements that just want to procreate as much as possible, and they co-opt bacteria to do that. That is scary for us because the plasmids are very efficient at collecting antibiotic resistance. So as they reproduce and infect more bacteria, they spread drug resistance."
While new antibiotics are always being discovered, they're only stopgap solutions, since bacteria will eventually just develop resistance to them as well. Plasmids, being a key mechanism for the spread of resistance, could be a good target for longer-lasting treatments.
So the Washington researchers set out to study plasmids in order to find a way to exploit them. They experimented on Acinetobacter baumannii, a bacteria that currently sits at the top of the World Health Organization's priority list due to the fact that it's now resistant to all major antibiotics.
The study found some intriguing results. As a self-defense mechanism, Acinetobacter kills other bacteria that get too close, which doesn't help the plasmids reproduce. So, the plasmids force their hosts to lay down their arms, allowing them to then pass copies of themselves into the neighboring bacteria.
In response, the researchers mutated the plasmids so they couldn't stop the bacteria from defending itself. In another test, they mutated the Acinetobacter itself so its defenses couldn't be lowered, and in both cases the outcome was the same. The plasmids – and by extension, antibiotic resistance – were unable to spread.
While they may have uncovered a chink in the armor, genetically engineering bacteria isn't exactly practical in a real world setting. But the study was a proof of concept, and now the team says it's a matter of finding a way to replicate those effects with compounds that could go into future disinfecting products.
"If we found an inhibitor, we could clean hospital surfaces with it and prevent the dissemination of drug resistance," says Feldman. "This is an out-of-the-box idea, but it's what we need. If we just find new antibiotics, the bacteria will just become resistant again. We need to find therapies that don't kill the bacteria but prevent it from becoming drug-resistant, so we can continue using our antibiotics into the future."
The research was published in the journal Proceedings of the National Academy of Sciences.